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Excess sitting linked to coronary artery calcification

Excess sitting linked to coronary
artery calcification, an early indicator of heart problems

Date: March 5, 2015

Source:

American College of Cardiology

Sitting for many hours per day is
associated with increased coronary artery calcification, a marker of
subclinical heart disease that can increase the risk of a heart attack,
according to research scheduled for presentation at the American College of Cardiology's
64th Annual Scientific Session in San Diego.

Coronary artery disease is the
most common type of heart disease and the leading cause of death in the United
States.

The study found no association
between coronary artery calcification and the amount of exercise a person gets,
suggesting that too much sitting might have a greater impact than exercise on
this particular measure of heart health.

The results suggest that exercise may
not entirely counteract the negative effects of a mostly sedentary lifestyle on
coronary artery calcium.

"It's clear
that exercise is important to reduce your cardiovascular risk and improve your
fitness level," said Jacquelyn Kulinski, M.D., assistant professor of
cardiovascular medicine at the Medical College of Wisconsin and the study's
lead author.

"But this study suggests that reducing how much you sit every
day may represent a more novel, companion strategy (in addition to exercise) to
help reduce your cardiovascular risk."

The research comes on the heels of
recent studies linking excess sitting with an increased risk for cardiovascular
disease, diabetes, cancer and early death.

The phenomenon has been dubbed
"sitting disease," though it is a lifestyle risk factor and not a
true medical condition.

This study offers a unique
perspective on the effects of sedentary behavior because it links sitting with
an early marker for heart disease risk, laying the foundation for future
studies that could investigate whether changing your habits could potentially
reverse the damage before you develop full-blown heart disease.

Coronary artery calcification,
measured through a non-invasive CT heart scan, indicates the amount of calcium
contained in plaques within the heart's arteries.

Coronary artery disease
occurs when such plaques accumulate over time, causing the arteries to narrow.

Analyzing heart scans and physical
activity records of more than 2,000 adults living in Dallas, the researchers
found each hour of sedentary time per day on average was associated with a 14
percent increase in coronary artery calcification burden.

The association was
independent of exercise activity and other traditional heart disease risk
factors.

"I think the
study offers a promising message. Reducing the amount of time you sit by even
an hour or two a day could have a significant and positive impact on your
future cardiovascular health," Kulinski said.

A particular strength of the study
is that the researchers used a motion-tracking device called an accelerometer
to measure how long participants were sedentary and how much they exercised,
whereas most previous studies have relied on surveys.

The results revealed participants
sat for a little more than five hours per day on average, with a range of two
to 12 hours. More sedentary participants were more likely to be older, have a
higher body mass index, and have diabetes or hypertension.

The analysis
accounted for these factors, as well as for income, marital status, smoking,
cholesterol, and other demographic and health-related factors. People with
known cardiovascular disease, such as a previous stroke or heart attack, were
excluded from the analysis.

"The lesson
here is that it's really important to try to move as much as possible in your
daily life; for example, take a walk during lunch, pace while talking on the
phone, take the stairs instead of the elevator and use a pedometer to track
your daily steps," Kulinski said. "And if you do have a very
sedentary job, don't go home at night and sit in front of the TV for hours on
end."

Story Source:

The above story is based on
materials provided by American College of Cardiology. Note: Materials may be
edited for content and length.

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Cite This Page:

American College of Cardiology.
"Excess sitting linked to coronary artery calcification, an early
indicator of heart problems." ScienceDaily. ScienceDaily, 5 March 2015.

<www.sciencedaily.com/releases/2015/03/150305205959.htm>.

Is Calcium Good or Bad?

George D. Lundberg, MD

February 03, 2015

Hello and welcome. I am Dr George
Lundberg and this is At Large at Medscape.

How is your calcium? Is it good or
bad? Does it help you or hurt you? Where is it? Evaluating calcium in humans is
a lot like evaluating a piece of real estate: It is all about location, location,
location.

First, the good places: More than 99%
is in teeth, bones, or blood and intra- and extracellular fluid.

Then, the bad places: soft tissues;
kidneys and urinary tract; artery and vein walls; tumors; female breasts; or as
part of resolving necrosis or cellular degeneration.

How does it get there? Calcium in,
calcium out. Calcium in: maybe a supplement of 1000 mg/day orally for an adult.
Calcium out: via urine and feces, with the retained calcium being managed by
spectacular metabolic homeostasis. It is a very delicate balance.

One of the ways that calcium
appears in seemingly unwanted locations is called "dystrophic
calcification," and its presence seems relatively inert.

Can you move calcium around in the
body? Maybe not moving individual calcium moieties from place to place, but can
you regulate how much of what kind of calcium is in any one place at any one
time?

Like the Blind Man and the
Elephant: Point of View Matters

• The
nutritionists would say: This is all about diet.

• The endocrinologists
would say...a lot; they really know this field.

• The
imagers would say: I love calcium; it gives me so many fun things to look at, measure,
and analyze to try to predict importance.

• The
urologists would say: I can take care of your stones. We will flush them out or
pluck them out or shake them into small pieces with the lithotripter.

And by
the way, here is your $30,000 bill.

• The
mammographers and breast surgeons would say: If I did not have calcium flecks
to find in the mammogram, I might have a really hard time justifying biopsies.

• The
procedural interventionists would say: Send me your calcified arteries; I have
a stent for you.

• Big
pharma would say: We have lots of drugs.

• The
outlier chelationists would say: We can give you some IV infusions to get rid
of all that bad stuff.

As a pathologist, I have cut—or, more
accurately, sawed—a whole lot of bones, healthy and diseased. It is really good
to have a lot of calcium as hydroxyapatite there, in the bone. I have cut up a
lot of kidneys destroyed by stones obstructing the urinary tract. Calcium can
be really bad to have there.

I have longitudinally opened or perpendicularly
transected many hundreds of large and small arteries; many normal, many
diseased by narrowing; many occluded by atherosclerotic plaque, intraplaque
hemorrhage, cholesterol, thrombus (acute, evolving, organized, or recanalized),
and calcified; sometimes very thick, hard, brittle, even rigid; and especially
in arteries of hearts, brains, necks, chests, bellies, legs. Bad.

But which came first: the chicken
or the egg? Was the vascular wall calcium an instigating progenitor, a fellow
traveler as simple dystrophy, a part of the inflammatory pathogenesis, or a
culminating bony add-on for advanced atherosclerosis? Those are really good
questions.

Here's the new stuff. A large
volume of alternative literature has been hyping vitamin K2 as active in
preventing or treating arterial calcification for years. But serious science
now seems to be backing that up.

The relationship of vitamin D, vitamin K2, and
calcium may hold a real key to a better understanding of harmful arterial
calcification. Check it out; keep an open mind; stay tuned.

Pneumonia May Be Worsened by Acid Suppressive Therapy

CLINICAL CONTEXT

Proton pump inhibitors (PPIs) are
effective and generally safe medications for patients with acid-related
disorders. However, this drug class has come under scrutiny in recent years
because of potential adverse effects associated with long-term use.

Corleto and
colleagues addressed the potential dangers of PPIs in a review published in the
February 2014 issue of Current Opinion in Endocrinology, Diabetes, and Obesity.

They found that PPIs were certainly associated with hypomagnesemia. However, they
noted that the evidence that PPIs may increase the risk for fracture was fairly
weak. Moreover, only limited evidence suggests that PPIs may promote a higher
risk for infection with Clostridium difficile. However, the risk for
microscopic colitis appears elevated among patients who use PPIs, even for a
short amount of time.

This review was largely dismissive
of the potential for serious risks associated with the use of PPIs, but there
is little doubt that PPIs remain one of the most overused of all prescribed
medications.

In a study of PPI prescriptions by hospitalists, Eid and
colleagues found that only 39% of these prescriptions followed published
guidelines for PPI use among inpatients. This research, which was published in
Internal Medicine in 2010, found that the most common erroneous indication for
providing PPIs was prophylaxis against gastrointestinal tract bleeding.

Physicians
in academic centers were more likely to adhere to PPI-prescribing guidelines, and
an inappropriate PPI prescription in the hospital was associated with a higher
chance of being prescribed a PPI, probably inappropriately as well, as an
outpatient.

The current study by Bhattarai and
colleagues, results which were presented at the 2014 AmericanCollege
of Chest Physicians Meeting, evaluates another potential risk associated with
gastric acid suppression: community-acquired pneumonia.

STUDY SYNOPSIS AND PERSPECTIVE

Acid suppressors are associated
with more severe community-acquired pneumonia, according to a study performed
at an inner-city hospital. However, comorbidities such as diabetes and chronic
obstructive pulmonary disease (COPD) could have played a role in the results.

"I looked through the literature and found there
was a high association between acid suppression and ventilator-associated
pneumonia," chief resident Bikash Bhattarai, MD, who is now a pulmonary
fellow at the Interfaith Medical Center in Brooklyn, New York, told Medscape
Medical News.

Previous research has shown that
acid suppression can increase susceptibility to community-acquired pneumonia, possibly
because reducing gastric acid secretion enhances colonization of the upper
gastrointestinal tract with oral bacteria.

However, none of the participants
in those studies were black. "We have a huge African American population, so
that's what prompted me to do the study," Dr Bhattarai explained here at
CHEST 2014.

His team conducted a retrospective
analysis to determine whether there was also an association between acid
suppression and severity of community-acquired pneumonia.

The researchers analyzed all
patients with community-acquired pneumonia admitted to their inner-city
hospital from 2010 to 2013. Patients who were suspected of having aspiration
pneumonia or who were immunosuppressed in any way were excluded from the analysis.

In the study cohort, 86% of
patients were black and 53% smoked. Although there were no fundamental
differences in demographic characteristics, there was more use of acid
suppression at the time of hospital admission in patients with certain
comorbidities.

Table 1.
Association Between Acid Suppression and Comorbidities

Comorbidity

Acid
Suppression (n = 468), %

No Acid
Suppression (n = 398), %

COPD

27.1

22.4

Diabetes mellitus

38.9

28.6

Previous stroke

14.1

8.5

Cancer

12.2

7.3

Chronic kidney disease

28.4

22.6

Physicians are very comfortable prescribing acid suppression. In fact, one meeting attendee said that the proportion of patients with community-acquired pneumonia taking acid suppressors was surprisingly low (46%). However, the results of the study suggest that the agents should be used more judiciously, said Dr Bhattarai.

"Even when the patient comes to the hospital, I'm not very comfortable discontinuing the acid suppressors, and my reflex is to put them on the medication if they're not on it already.

But we shouldn't give these medications if they aren't indicated because there are risks," he said.

There was also an association between acid suppression and indicators of the severity of community-acquired pneumonia, some of which fell just short of statistical significance.

Table 2. Link Between Acid Suppression and Severity of Pneumonia

Indication of
Severity

Acid
Suppression (n = 468)

No Acid
Suppression (n = 398)

P Value

Positive blood culture result (%)

12

5.5

< .001

Thrombocytopenia (%)

22

17

< .001

Radiologic pneumonia (%)

94

93.7

Length of hospital stay (days)

10.51

8.96

.057

Mortality (%)

15.1

11.5

.057

Still, not everyone is convinced by the data. The study was observational and relatively small, and confounding factors might explain the results, according to Punginathn Dorasamy, MB ChB, professor of medicine at McMaster University in Hamilton, Ontario, Canada, who attended the presentation.

He pointed out that previous research has yielded conflicting results and, in one case, the study authors suspected that patients receiving acid suppressors had preexisting conditions that predisposed them to pneumonia.

"It's difficult to say that acid suppression is contributing to the worsening of the pneumonia. But there may be a message that in a small subset of patients, such as those with diabetes or COPD, if we are suppressing the acid, we may increase the risk of severe types of pneumonia," Dr Dorasamy told Medscape Medical News.

The study was conducted as a retrospective
analysis of cases in an inner-city community hospital in New York City.

Researchers collected data regarding patients
admitted for community-acquired pneumonia between 2011 and 2013. Patients with
suspected aspiration pneumonia and those with HIV infection were excluded from
analysis.

The main study outcomes were the effects of
acid suppression on the severity and outcomes of community-acquired pneumonia. Researchers
used a regression analysis to account for other variables separating the 2 study
groups.

 866
patients were included in the
analysis. An estimated 48% of patients were men, and 86% were African American.

 54%
of the study sample had received
acid suppressive therapy.

Demographic variables were not significantly
associated with the use of acid suppressive therapy, but patients with more
comorbidity, including COPD, diabetes mellitus, previous stroke, or cancer were
more likely to receive acid suppressive treatment.

Rates of positive blood culture results were
higher among patients who received acid suppressive therapy vs those who did
not (12% vs 5.5%, respectively). The respective rates of thrombocytopenia were 22%
and 17%. Both of these differences were statistically significant.

However, the rates of radiologic evidence of
pneumonia were similar and were above 90% regardless of acid suppressive therapy.

The average lengths of hospital stay among
patients who did and did not receive acid suppressive therapy were 10.51 and 8.96
days, respectively. The respective rates of mortality were 15.1% and 11.5%. Both
of these differences just missed statistical significance.

CLINICAL IMPLICATIONS

Good evidence exists that PPIs are widely
overused among inpatients. However, a review found weak evidence that PPIs may
adversely affect bone health or increase the risk for infection with C
difficile. PPIs do promote hypomagnesemia.

The current study by Bhattarai and colleagues
suggests that adults using acid suppressive therapy are more likely to have
severe community-acquired pneumonia and experience longer lengths of hospital
stay and higher rates of mortality.

http://www.medscape.org/viewarticle/835533?nlid=75425_2712&src=cmemp

Aspirin Ineffective in Preventing Cardiovascular Disease

CLINICA CONTEXT

Although cardiovascular disease is the number one cause of mortality in the developed world, the impact of cardiovascular disease from region to region can be heterogeneous. Therefore, it is important to understand trends in cardiovascular disease from a geographic and cultural perspective.

Hata and colleagues did just that in evaluating trends in cardiovascular disease and risk factors in Japan.

Their research, which was published in the September 10, 2013, issue of Circulation, demonstrated that certain risk factors, such as blood pressure control among patients with hypertension and the overall rate of smoking, improved in the general Japanese population in the 4 to 5 decades between the 1960s and 2000s. However, these positive changes were counterbalanced by a strong increase in rates of obesity, hyperlipidemia, and glucose intolerance during the same period.

Overall, these diverging trends resulted in no substantial change in the rate of myocardial infarction (MI) through the decades, although rates of mortality from stroke were reduced because of lower stroke incidence and better stroke management.

Could aspirin as primary prophylaxis help to reduce the risk for cardiovascular disease in Japan? The current study by Shimada and colleagues yields results with clear implications for the management of all adults worldwide.

STUDY SYNOPSIS AND PERSPECTIVE

A new trial shows no benefit of low-dose, once-daily aspirin in the primary prevention of cardiovascular events in patients with multiple risk factors, including hypertension, diabetes, and dyslipidemia.

No benefit was seen for the composite endpoint of nonfatal MI, nonfatal stroke, or death from cardiovascular causes. There were significant reductions in MI and in transient ischemic attack (TIA), but a significant increase in serious extracranial hemorrhage meant that the net benefit was questionable.

The overall rate of events was much lower than anticipated in this study, and it did not reach statistical significance, said study coauthor Kazuyuki Shimada, MD, Department of Cardiology, Shin-Oyama City Hospital, Tochigi, Japan. "Therefore, the possibility that aspirin does have a beneficial effect in this population cannot be excluded."

Still, the clinical importance of aspirin for primary prevention was "less than originally anticipated in this population," he concluded, and further analyses are planned to see whether they can identify patients who may benefit most from aspirin.

"Lastly, it will be interesting to see if the ongoing studies ARRIVE, ASCEND, ASPREE, and ACCEPT-D, which are assessing primary prevention in predominantly Western populations, have different outcomes to our study in Japanese patients," Dr Shimada said.

The results of the Japanese Primary Prevention Project (JPPP) were published online November 17 in JAMA to coincide with presentation here at the American Heart Association 2014 Scientific Sessions.

Primary Prevention

For the last several years, the benefits and risks associated with aspirin for primary prevention of cardiovascular events for those at moderately increased risk have been "hotly debated," Dr Shimada said. "Recently the FDA [Food and Drug Administration] cautioned against the general use of aspirin for the primary prevention of heart attacks and strokes," he noted. An FDA release on May 5 concluded that after a review of the literature, the evidence does not support the use of aspirin for primary prevention.

"In order to inform our decision making in Japan and to develop country-specific recommendations, we conducted the Japanese Primary Prevention Project study, which prospectively evaluated daily, low-dose aspirin in the primary prevention of CV [cardiovascular] events in elderly Japanese patients with cardiovascular risk factors," Dr Shimada said.

The JPPP was a multicenter, open-label, randomized, parallel-group trial. Using a Prospective Randomized Open Blinded Endpoint study design, patients with hypertension, dyslipidemia, and/or diabetes mellitus without a history of cardiovascular disease were enrolled during routine visits to their primary care provider at one of 1007 clinics in Japan between March 2005 and June 2007.

A total of 14,658 patients were randomly assigned to receive 100 mg of enteric-coated aspirin per day or no aspirin, along with continuous management of their other risk factors. Patients were to be monitored for up to 6.5 years, with last follow-up in May 2012. Study outcomes were adjudicated by an expert panel blinded to treatment assignments.

"At the time of the second interim analysis in May 2011, the independent data monitoring committee recommended that the study was to be discontinued at the next annual study assessment due to futility and to avoid unnecessary risk of adverse events," he said. At the time of study discontinuation, patients had been followed up for a median of 5.02 years (interquartile range, 4.55 - 5.33 years).

The primary outcome was a composite of death from cardiovascular causes (MI, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal MI. Secondary outcomes included those events plus TIA, angina pectoris, and atherosclerotic disease requiring surgery or intervention, as well as each individual outcome.

A total of 56 fatal events occurred in each group. Nonfatal stroke occurred in 117 patients in the aspirin group and 114 in the no-aspirin group. Nonfatal MI was seen in 20 patients taking aspirin vs 38 in the no-aspirin group, and undefined cerebrovascular events occurred in 3 patients receiving aspirin vs 5 patients not receiving aspirin.

"There was no statistically significant difference between the two groups in time to the primary end point," Dr Shimada reported. "The hazard ratio indicates that there was an insignificant 6% reduction in the risk of a primary end point event in the aspirin group vs the no-aspirin group."

Table.
JPPP: Main Outcomes

End Point

Aspirin

No Aspirin

Hazard Ratio
(95% Confidence Interval)

>PValue

Five-year cumulative event rate (%)

2.77 (2.40 - 3.20)

2.96 (2.58 - 3.40)

0.94 (0.77 - 1.15)

.54

Nonfatal MI

0.30 (0.19 - 0.47)

0.58 (0.42 - 0.81)

0.53 (0.31 - 0.91)

.02

TIA

0.26 (0.16 - 0.42)

0.49 (0.35 - 0.69)

0.57 (0.32 - 0.99)

.04

Extracranial hemorrhage requiring transfusion or hospitalization

0.86 (0.67 - 1.11)

0.51 (0.37 - 0.72)

1.85 (1.22 - 2.81)

.004

The risk for a primary end point
event did not differ significantly for aspirin vs no aspirin in any of the
disease risk factor subgroups assessed, including hypertension vs no
hypertension, dyslipidemia vs no dyslipidemia, diabetes vs no diabetes, and family
history vs no family history, or by demographic factors such as age and gender.

For most secondary end points, there
was no significant difference between the treatment groups. However, nonfatal
MI was significantly reduced by 47% with aspirin vs no aspirin, and TIA was
reduced by a significant 43%, Dr Shimada said.

"Conversely, there was a significant increase in
serious extracranial hemorrhage in the aspirin group -- the hazard ratio
indicates an 85% increase in such events," he said. "Therefore, any benefits
of aspirin in terms of the reduced risk of nonfatal MI and TIA must be
counterbalanced with consideration of the significantly increased risk of
serious extracranial hemorrhage."

Finally, there was a prespecified
analysis of gastrointestinal (GI) adverse events in the randomly selected
population. "The results clearly indicate that aspirin is associated with
an increased incidence of these GI events, the known side-effect profile of
aspirin, although the study was unblinded and these were not primary or
secondary analyses," he said.

Less Power, Increasing Challenge

In an accompanying editorial, J. Michael
Gaziano, MD, MPH, Veterans Affairs Boston Healthcare System, Brigham and Women's
Hospital, Harvard Medical School, Boston, Massachusetts, and associate editor
of JAMA, and Philip Greenland, MD, Departments of Preventive Medicine and
Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois,
and senior editor of JAMA, point to the lower-than-expected event rate in this
study, "leading to a study with less power to detect differences in the
primary outcome than anticipated."

Aspirin primary prevention trials
have "become increasingly challenging to conduct," they write. "There
is wider use of a number of prevention medications such as antihypertensive
agents and lipid-lowering drugs, as well as other preventive measures that
collectively result in fewer events than expected, as seen in JPPP."

The findings add to the "body
of evidence that helps refine the answer to the question of when aspirin should
be used to prevent vascular events," they say. "Decision making
involves an assessment of individual risk-to-benefit that should be discussed
between clinician and patient."

In some situations the benefit of
aspirin is clear, such as those at high short-term risk after an acute vascular
event, or those undergoing certain vascular procedures, they add. "On the
other hand, patients at very low risk of vascular events should not take
aspirin for prevention of vascular events, even at low dose."

In the middle are those without
overt vascular disease but risk levels approaching those with cardiovascular
disease. "It remains likely that there is some level of risk of CVD [cardiovascular
disease] events that would result in a positive trade-off of benefit and risk
for the use of aspirin, but the precise level of risk is uncertain. This is in
part because most populations studied have been at very low risk."

The editorialists also point to
the ongoing ASCEND, ARRIVE, and ASPREE studies to help refine guidelines in
higher-risk patients.

"Findings from these studies, with additional
data about risks and other potential long-term benefits, such as reducing the
risk of colorectal and other cancers, will prove helpful for clinical decision
making involving the role of aspirin for primary prevention," Dr Gaziano
and Dr Greenland conclude.

End of the Road?

At the meeting here, Dorairaj
Prabhakaran, DM, vice president and professor of epidemiology, Public Health
Foundation of India, and professor of epidemiology, London School of Hygiene
and Tropical Medicine, United
Kingdom, was the invited discussant for this
trial. He considered the question of whether these findings spell the "end
of the road for aspirin in primary prevention."

Among the reasons the trial was
negative were the lack of power because of early termination, he said, and the
fact that aspirin on a background of widespread statin use may make it
difficult to show a benefit.

"Benefit is very unlikely in low-risk
populations such as those with less than 1% events per year," Dr
Prabhakaran said. "There could be a role in special groups, particularly
younger populations that are not being evaluated well from low-/middle-income
countries like India,
where the risk of coronary artery disease is extremely high."

Risk scores are needed for these
countries to identify high-risk people, he added, and "we also await the
results of other studies in primary prevention," such as the TIPS-2 trial
in India
that combines a "polypill" with aspirin, he noted.

If risk is less than 10%, benefit
is unlikely, but there is a "gray area" between 10% and 20% where
benefit may yet be seen with aspirin for primary prevention, he said (J Am Coll
Cardiol. 2014;64:319-327).

He quoted Sir Richard Doll, who
once said, "Death is inevitable, but premature death is not."

"In reducing premature death, aspirin is the
most inexpensive option and we should pursue with vigor in identifying
individuals and populations who may benefit," Dr Prabhakaran concluded.

During a discussion after the
presentation, Christopher Cannon, MD, HarvardMedicalSchool, pointed out that
in his practice, many patients arrive having already started aspirin therapy on
their own, "whereas we're seeing there's an active decision of benefit and
risk that needs to be taken.

"It's a serious decision whether to start
aspirin, so this is a terrific reminder that we really need to calculate based
on risk and see could this be of benefit, or would there be more harm?" he
added.

The JPPP was sponsored by the
Japanese Ministry of Health, Labor, and Welfare and the Waksman Foundation of
Japan. Enteric-coated 100-mg aspirin tablets were provided free of charge by
Bayer Yakuhin. Dr Ikeda discloses receiving fees for medical advice from
AstraZeneca, Bayer, Daiichi Sankyo, GlaxoSmithKline, and sanofi-aventis. Disclosures
for coauthors appear in the publication.

The study was designed as an open-label
clinical trial. Participants were recruited from 1007 primary care offices in Japan between 2005
and 2007.

Patients eligible for study participation were
between 60 and 85 years old and had no history of cardiovascular events. However,
all participants had hypertension, hyperlipidemia, or diabetes.

Participants were randomly assigned to receive
aspirin 100 mg daily or no aspirin. Their ongoing treatment was otherwise
unchanged, save for the fact that they were prohibited from using other
antiplatelet or anticoagulant drugs.

Study outcomes were reported by the primary
care clinics to the central research team. The primary study outcome was a
composite of cardiovascular death, nonfatal stroke, and nonfatal MI. Researchers
also followed rates of TIA and angina pectoris. Finally, rates of adverse
events such as bleeding and GI complications were measured.

The study analysis evaluated the efficacy of
aspirin in the context of participants' total cardiovascular risk profile.

The study was complicated by a lower rate of
incident cardiovascular events. By 2011, only 290 primary end point events had
occurred among the 14,658 patients enrolled in the study, although researchers
had increased enrollment in their first interim analysis.

The median age of the 14,658 study participants
was 70 years. An estimated 58% of the study cohort consisted of women, 85% of
participants had hypertension, 72% had hyperlipidemia, and 34% had diabetes. Approximately
13% of the cohort consisted of current smokers.

Adherence to aspirin therapy was fair overall, with
values of 88.9% at year 1 of the study and 76.0% in year 5.

Nearly 10% of patients in the control group
began aspirin therapy by year 5, and 10% of patients in both cohorts received
other antiplatelet or anticoagulant medications by year 5.

The study steering committee prematurely
stopped the research after a median follow-up period of 5.02 years because of a
lack of efficacy of aspirin in preventing the primary study outcome.

At 5 years, the respective rates of incident
cardiovascular outcomes in the aspirin and no-aspirin groups were 2.77% and 2.96%.
The estimated hazard ratio (HR) for the primary outcome in comparing the
aspirin group vs the no-aspirin group was 0.94 (95% CI, 0.77 - 1.15).

Subgroup analysis based on age, gender, and the
presence of different cardiovascular risk factors failed to yield any
significant advantage for aspirin therapy.

Adding TIA and angina pectoris to the main composite
outcome also failed to demonstrate any significant benefit for aspirin therapy.

The overall mortality rate was similar in the
aspirin and no-aspirin cohorts.

A previous study by Hata and colleagues of
trends in cardiovascular disease in Japan from the 1960s to the 2000s
demonstrated improved hypertension control and lower rates of smoking, which
was counterbalanced by higher rates of obesity, glucose intolerance, and
hyperlipidemia. Overall, the risk for MI remained stable during this period, although
the risk for stroke improved.

The current study by Shimada and colleagues
demonstrates that aspirin may be ineffective as primary cardiovascular
prevention among older adults at elevated risk for cardiovascular disease. Aspirin
was effective in preventing nonfatal MI and TIA but did not improve mortality
outcomes and promoted a higher risk of serious extracranial bleeding.